An Investigation of Norpropoxyphene Cyclization in Methanol
Authors: Huahua Jian PhD, Sandra Ybarra, Derrell Johnson MS, Isil Dilek PhD and Uma Sreenivasan PhD
Presented at SOFT, October 2009
Abstract
Dextropropoxyphene, a synthetic opioid analgesic, is widely prescribed for the relief of mild to moderate pain. It is primarily metabolized to norpropoxyphene in humans through N-demethylation. In most methods, analysis of norpropoxyphene involves a strong base-catalyzed conversion to norpropoxyphene amide to help improve the chromatography.
The solution behavior of norpropoxyphene in the prescence and absence of base was examined by HPLC, LC/MS, and 1H NMR. The results support the formation of a cyclic intermediate in solution. Literature precedence exists for the involvement of a cyclic intermediate in the base-catalyzed conversion of norpropoxyphene to norpropoxyphene amide as well as in the formation of cyclic dinorpropoxyphene.
We propose a mechanism for the formation of this cyclic intermediate and its impact in the analysis of norpropoxyphene by LC/MS. We offer HPLC and 1H NMR evidence which corroborate the formation and time of the formation of this cyclic intermediate in solution will also be discussed.
The solution behavior of norpropoxyphene in the prescence and absence of base was examined by HPLC, LC/MS, and 1H NMR. The results support the formation of a cyclic intermediate in solution. Literature precedence exists for the involvement of a cyclic intermediate in the base-catalyzed conversion of norpropoxyphene to norpropoxyphene amide as well as in the formation of cyclic dinorpropoxyphene.
We propose a mechanism for the formation of this cyclic intermediate and its impact in the analysis of norpropoxyphene by LC/MS. We offer HPLC and 1H NMR evidence which corroborate the formation and time of the formation of this cyclic intermediate in solution will also be discussed.